There are marked changes in skeletal and periodontal tissues during pregnancy and lactation and after menopause in women. During pregnancy, there is an accumulation of mineral and some increase in skeletal mass. Chronic inflammatory diseases are often aggravated during pregnancy (e.g. gingivitis). During lactation, there are dramatic changes in mineral and osseous tissue metabolism, including an apparent transient loss of skeletal mass. The decline in osseous tissues after the menopause is well recognized (e.g. post-menopausal osteoporosis). It is now apparent that even with marked changes in mineral and skeletal metabolism during pregnancy and lactation, that reproductive cycles have a protective effect on the longer term integrity of osseous tissues in women. The proposed experiments will continue to define the changes in, and mechanisms for, skeletal, mineral, and soft-tissue alterations during pregnancy, lactation and after cessation of ovarian function. Tissue-level morphometry studies will address new hypotheses on the role of bone remodeling and modeling while mechanistic studies will examine specific putative endocrine regulators. To address these issues, the following objectives are proposed. To determine if the anabolic changes during pregnancy are due to the initiation of remodeling coherence by the suppression of bone remodeling with increased bone modeling. This may provide the first evidence for a physiological reversible mineral accumulation in a mammalian skeleton. To determine the role of growth hormone-related peptides, specifically placental lactogens, proliferin and prolactin, on osseous tissues during pregnancy. The production of these hormones is increased in pregnancy and they may have roles in skeletal and mineral metabolism. To determine if the decidua in the absence of a placenta has an influence on mineral and skeletal metabolism during pseudopregnancy. Possible somatogenic effects of decidualization will be defined in this study. To determine the role of relaxin in periodontal soft tissues, specifically the periodontal ligament, during pregnancy. Relaxin in known to affect fibrous joints and have systemic effects and is postulated as having a role in observed changes in periodontal tissues in later pregnancy. To determine if the changes in skeletal metabolism during lactation are due to a transient increase in bone remodeling, resulting in a reversible mineral deficit. Data from this study might help explain the apparent protective effect of lactation on longer term bone health in women. The final study will determine if the patterns of bone loss during lactation, when compared with ovariectomy, are such to maximize skeletal reconstitution. Collectively these studies will define tissue-level changes during pregnancy and lactation, and define the roles of specific endocrine regulators.